Over the past decade, dihydropyridine calcium antagonists have become widely known therapeutic agents having vasodilator properties which can be used as antihypertensives and coronary agents. More recently, it has been found that small structural modifications produce dihydropyridines with effects diametrically opposed to those of calcium antagonists. In contrast to the calcium antagonists, dihydropyridines such as Bay K8644 and CGP28392 promote an influx of calcium ions, therefore producing positive inotropic and vasoconstrictor effects. Bay K8644 is more than 10 times as potent as a calcium agonist than CGP28392. However, Bay K8644 is toxic because it causes coronary vasoconstriction and therefore it is only useful as a therapeutic tool to ascertain the function of calcium entry blockers but is not useful in therapeutics as a cardiotonic. ##STR2##
Representative of the art in the field of dihydropyridine calcium agonists are U.S. Pat. No. 4,248,873 issued Febr. 3, 1981, published European Patent Application No. 0071819, U.S. Pat. Nos. 4,537,881 issued Aug. 27, 1985 and 4,532,248 issued July 30, 1985 amongst others. Literature references include M. Schram, et al., Nature, 303, 535 (1983); M. Schram et al., Arzneim-Forsch., 33, 1268 (1983); P. Erne et al., Biochem. Biophys. Res. Commun., 118, 842 (1984).
Combining calcium agonist properties and alpha.sub.1 -adrenergic blocking properties in a single molecular structure provides a new and attractive principle for the treatment of congestive heart failure. The combination of these two principles provides a novel class of cardiotonics which have minor cardiac stimulatory effects in combination with pronounced vasodilator properties. The detrimental vasoconstricting properties which are normally associated with dihydropyridine calcium agonists are minimized by including the alpha.sub.1 -adrenergic blocking properties which cause dilation of the peripheral vasculature.